Drug for treating tumor diseases and having antibacterial antivirus anti-inflammatory effects

ABSTRACT

The present disclosure describes an anti-cancer drug for treating tumor diseases and providing antibacterial, antivirus, and anti-inflammatory effects. The drug contains a naphthalene dicarboxamide compound with a structural formula as shown in Formula I or a biologically acceptable salt or ester form of the compound with the formula I as an active ingredient. The drug is able to help inhibit the growth of tumor cells and possesses certain antibacterial, antivirus, and anti-inflammatory effects.

FIELD

The present disclosure is in the field of biomedicine, chemistry,medicine, microbiology, and drug production, especially for tumor andcancer treatment.

BACKGROUND

With the fast pace of modern society and high pressure in daily work,many people are suffering in a suboptimal health status (SHS). Aninsufficiency of autoimmunity leads to increasing incidences of variousdiseases, which seriously threaten people's lives. Since the 20thcentury, organic chemical synthesis has played a vital role for novelsmall molecules discoveries to treat various diseases due to theirunique spatial stereo structure, electronic distribution, and spatialarrangement of active groups.

Naphthalene diamides are based on naphthalene rings as a parent nucleus,connecting with two amide bonds. It can interact electrically withenzymes and receptors related to cancer in organisms through theinteraction of amides and electron-rich groups. Meanwhile, aromaticrings in the structure can stack with enzymes and receptors to inhibitthe occurrence of cancer.

SUMMARY

The present disclosure describes a naphthalene diamide compoundcomprising a structure expressed by the following structural formula, asynthesis method of preparing the compound, and in vitro anti-tumor cellactivity screening studies.

In another aspect, the present disclosure describes a pharmaceuticalcompound or composition for treatment of cancer and a drug containingthe naphthalene dicarboxamide compound with the structural formula asshown below or a biologically acceptable salt or ester with saidcompound as an active ingredient. The anti-cancer drug is able toinhibit the growth of tumor cells and has certain antibacterial,antiviral, and anti-inflammatory effects.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an ABC-09 nuclear magnetic resonance spectrum of thecompound and/or drug of the present disclosure.

FIG. 2 illustrates an ABC-46 nuclear magnetic resonance spectrum of thecompound and/or drug of the present disclosure.

DETAILED DESCRIPTION

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the disclosure.As used herein, the term “and/or” includes any and all combinations ofone or more of the associated listed items. As used herein, the singularforms “a,” “an,” and “the” are intended to include the plural forms aswell as the singular forms, unless the context clearly indicatesotherwise. “they”, “he/she”, or “he or she” or are used interchangeablybecause “they”, “them”, or “their” can now be used as singulargender-neutral pronoun in modern English. It will be further understoodthat the terms “comprises” and/or “comprising” when used in thisspecification, specify the presence of stated features, steps,operations, elements, and/or components, but do not preclude thepresence or addition of one or more other features, steps, operations,elements, components, and/or groups thereof. Unless otherwise defined,all terms (including technical and scientific terms) used herein havethe same meaning as commonly understood by one having ordinary skill inthe art to which this disclosure belongs. It will be further understoodthat terms, such as those defined in commonly used dictionaries, shouldbe interpreted as having a meaning that is consistent with their meaningin the context of the relevant art and the present disclosure and willnot be interpreted in an idealized or overly formal sense unlessexpressly so defined herein. In the description, it will be understoodthat a number of techniques and steps are disclosed. Each of these hasan individual benefit and each can also be used in conjunction with oneor more, or in some cases all, of the other disclosed techniques.Accordingly, for the sake of clarity, this description will refrain fromrepeating every possible combination of the individual steps in anunnecessary fashion. Nevertheless, the specification and claims shouldbe read with the understanding that such combinations are entirelywithin the scope of the disclosure and the claims.

In the following description, for purposes of explanation, numerousspecific details are set forth to provide a thorough understanding ofthe present disclosure. It will be evident, however, to one ordinarilyskilled in the art that the present disclosure may be practiced withoutthese specific details. The present disclosure is to be considered as anexemplification of the disclosure and is not intended to limit thedisclosure to the specific embodiments illustrated by the figures ordescription below. The present disclosure will now be described byreferencing the appended figures representing preferred or alternativeembodiments.

Some of the technical terms in the present disclosure are explained asfollows: Lower alkyl groups include, but are not limited to, methyl,ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl,N-pentyl, isoamyl, neopentyl, heji, heptyl. Halogens include fluorine,chlorinated, brominated, and iodine. C₁₋₁₂ alkyl includes, but is notlimited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl,tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-amyl,hexyl, heptyl, octyl, nonyl, decyl. C₁₋₇ alkyl includes, but is notlimited to, methyl, ethyl, propyl, Isopropyl, butyl, isobutyl,tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-amyl base,hexyl, heptyl, etc. Lower alkenyl groups include, but are not limitedto, vinyl, propylene, butenyl, pentenyl, hexenyl, heptenyl, hepene,octenyl. C₃₋₇ cycloalkyl groups include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl.

The present disclosure provides a naphthalene diamide compound with astructure expressed by Formula I, a synthesis method of preparing thecompound, and in vitro anti-tumor cell activity screening studies.

In another aspect, the present disclosure describes a pharmaceuticalcompound or composition for treatment of cancer and a drug containing anaphthalene dicarboxamide compound with a structural formula as shownbelow or a biologically acceptable salt or ester with said compound asan active ingredient. To achieve the above goals, the present disclosureprovides the following technical solutions: a naphthalene diamide basedchemical structure as shown in Formula I,

where X and Y can be separately selected from carbonyl, thiocarbonyl,and sulfonyl groups. R₁, R₂ together with adjacent nitrogen atoms canform a ring of 3 to 12 atoms or a ring structure substituted by asubstituent M.

Alternatively, R₁ and R₂ can be independently selected from hydrogen,C₁₋₁₂ alkyl, C₁₋₁₂ alkoxy, C₃₋₇ cycloalkyl, C₁₋₁₂ alkoxycarbonyl, C₁₋₁₂alkylcarbonyl, aminocarbonyl, C₁₋₁₂ alkylaminocarbonyl, nitro, oxazoly,thiazoly, pyridyl, pyridine, dihydropyridyl, tetrahydropyridyl,piperidinyl, thiazinyl, pyrrolyl, imidazolyl, pyrazolyl, pyrimidinyl,piperaziny, morpholinyl, furanyl, pyranyl, and other heterocyclicgroups. They can also be independently selected from the above-mentionedgroups, aryl groups, benzyl groups, aryl hydrocarbon group, andheteroaryl hydrocarbon group, which are selectively replaced bysubstituted group M. When R₁ and R₂ are replaced by substituent M, thenumber of substituent M can be single or multiple. If the substituents Mare multiple, they are not relevant to each other, or they form a ringstructure. If two substituents M form a ring structure and the linkedgroup substituted by substituent M is also a ring structure, they may ormay not form a heterocyclic ring structure.

Substitute M can be hydrogen, fluorine, chlorine, bromine, iodine,cyano, nitro, hydroxyl, amino, C₁₋₁₂ alkyl, halogenated C₁₋₁₂ alkyl,perfluoro-C₁₋₁₂ alkyl, polyhalogenated C₁₋₆ alkyl, aryl, substitutedaryl, C₁₋₁₂ alkylamino, C₃₋₁₂ cycloalkylamino, di(C₁₋₁₂ alkyl)amino,C₃₋₁₂ cycloalkyl, and substituted C₃₋₁₂ cycloalkyl.

The aryl hydrocarbon group substituted by the substituent M is ahalogenated halophenyl hydrocarbon, alkoxyalkyl, perfluoroalkylphenylhydrocarbon, hydrocarbyl-substituted phenyl hydrocarbon,nitro-substituted phenyl hydrocarbon, or hydroxyl-substitutedphenylhydrocarbyl.

The heteroaryl hydrocarbon group substituted by substituent M includeshalogenated pyridine hydrocarbon group, halogenated furan hydrocarbongroup, halogenated thiazolidine, halogenated pyrimidine hydrocarbyl,halogenated imidazolium, nitro-substituted pyridine hydrocarbon,nitro-substituted furanyl, nitro-substituted thiazolidine,nitro-substituted pyrimidine hydrocarbyl, nitro-substituted imidazolium,amino-substituted pyridine hydrocarbon group, amino-substituted furanhydrocarbyl, amino substituted thiazolyl, amino substituted pyrimidinehydrocarbyl, and amino substituted imidazolium.

R₃ can be selected from hydrogen, fluorine, chlorine, bromine, iodine,nitro, amino, C₁₋₃ alkyl, C₁₋₃ alkoxy, C₃₋₇ cycloalkyl, halogensubstituted C₃₋₇ cycloalkyl, halogenated C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl,hydroxyl-substituted C₁₋₁₂ alkyl, C₁₋₁₂ alkoxy, C₁₋₁₂ alkoxycarbonyl,aminocarbonyl, C₁₋₆ alkylaminocarbonyl, Di(C₁₋₁₂ alkyl)aminocarbonyl,C₃₋₇ cycloalkylaminocarbonyl, C₃₋₇ cycloalkoxy, hydroxy-C₁₋₁₂ alkoxy,halogenated C₁₋₁₂ alkoxy, amino C₁₋₁₂ alkyl, amino C₁₋₁₂ alkoxy, C₁₋₁₂alkyl sulfone, C₂₋₁₂ alkenyl sulfone, C₃₋₇ cycloalkyl sulfone,heterocyclic oxy, amino-substituted piperidinyl,N-methylpiperidin-4-carbonyl, piperazine-C₁₋₁₂ alkyl, formamide, andN-methyl piperidine carboxamide.

R₄ can be selected from hydrogen, C₁₋₁₂ alkyl, C₁₋₁₂ alkoxy, C₃₋₇cycloalkyl, halogen substituted C₃₋₇ cycloalkyl, C₁₋₆ alkoxycarbonyl,C₁₋₁₂ alkylcarbonyl, aminocarbonyl, C₁₋₁₂ alkylaminocarbonyl, nitro,amino, C₁₋₃ alkyl substituted amino, Di(C₁₋₃ alkyl) substituted amino,oxazolyl, thiazolyl, pyridyl, dihydropyridyl, tetrahydropyridyl,piperidinyl, thiazinyl, pyrrolyl, imidazolyl, pyrazolyl, pyrimidinyl,piperazinyl, morpholinyl, furanyl, pyranyl, and other heterocyclicgroups. The following groups can optionally be substituted by asubstituent Q: an aryl group, a benzyl group, a heteroaryl group, anarylalkyl group, and a heteroaryl hydrocarbon group. The substituent Qcan be double and multiple groups independently, which form ringstructures via molecular interconnections.

When each substituent Q is an independent substituent, each substituentQ can be separately selected from hydrogen, fluorine, chlorine, bromine,iodine, cyano, nitro, hydroxyl, amino, C₁₋₁₂ alkyl, halogenated C₁₋₁₂alkyl, perfluoro-C₁₋₁₂ alkyl, polyhalogenated C₁₋₁₂ alkyl, C₁₋₁₂ alkoxy,halogenated C₁₋₁₂ alkoxy, aryl, substituted aryl, C₁₋₁₂ alkylamino, C₃₋₇cycloalkylamino, Di(C₁₋₁₂ alkyl)amino, C₃₋₇ cycloalkyl, and substitutedC₃₋₇ cycloalkyl.

The numbers of R₅ and R₆ range from 0 to 6 while the optimal number is0-3 or 0-2. If there are more than two R₅ and R₆, they are independentof each other.

R₅ and R₆ are separately selected from hydrogen, fluorine, chlorine,bromine, iodine, cyano, nitro, hydroxyl, hydroxyl, C₁₋₁₂ alkyl, C₁₋₁₂alkoxy, C₃₋₇ cycloalkyl, halogenated C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl,hydroxyl-substituted C₁₋₁₂ alkyl, C₁₋₁₂ alkylamino, C₃₋₇cycloalkylamino, Di(C₁₋₁₂ alkyl)amino, amino-C₁₋₁₂ alkylamino, C₁₋₁₂alkoxy, C₁₋₁₂ alkylamino, C₁₋₁₂ alkoxycarbonyl, Di(C₁₋₁₂ alkoxy-C₁₋₁₂alkyl) amino, aminocarbonyl, C₁₋₁₂ alkylaminocarbonyl, Di(C₁₋₁₂alkyl)aminocarbonyl, C₃₋₇ cycloalkylaminocarbonyl, C₃₋₇ cycloalkoxy,halogenated C₁₋₁₂ alkoxy, amino C₁₋₁₂ alkyl, amino C₁₋₁₂ alkyl, C₁₋₁₂alkyl sulfone, C₂₋₁₂ alkenyl sulfone, C₃₋₇ cycloalkyl sulfone,halogenated C₃₋₇ cycloalkyl, heterocyclic oxy, piperidinylamino,N-methylpiperidin-4-carbonyl, piperazine-C₁₋₆ alkyl, formamide, andN-methyl piperidine carboxamide.

Further, X could be carbonyl, thiocarbonyl, or sulfonyl. Carbonyl ispreferred.

Further, Y could be carbonyl, thiocarbonyl, or sulfonyl. Carbonyl ispreferred.

Further, X substituents are in the β position of the naphthalene ringand N substituents (connected to Y, shown in Formula 1) are in thenon-substituted para-position of the naphthalene ring. For example, if Xis substituted at the 2-position, then Y-connected N is substituted atthe 6-position. If X is substituted at the 3-position, then Y-connectedN substituted at the 7-position. Numbered from the carbon next to thetwo symmetric carbon (the two carbons in the middle are not numbered),the carbons of 1, 4, 5, and 8 are the same (called α carbon, orα-position), while the carbons of 2,3, 6, 7 are the same (called βcarbon, or β-position).

Further, R₁ and R₂ together with the adjacent nitrogen atom can form apyrrole ring, tetrahydropyrrole ring, pyridine ring, tetrahydropyridinering, piperidine ring, piperazine ring, oxazine ring, tetrahydrooxazidering, morpholine ring. The ring structure formed above can besubstituted by C₁₋₆ alkyl, substituted C₁₋₆ hydrocarbyl substitution,halogenated C₁₋₃ hydrocarbon group substitution.

Further, R₁ and R₂ can be independently selected from hydrogen, C₁₋₆alkyl, C₁₋₆ alkoxy, cyclopropane, cyclohexane, C₁₋₄ alkoxycarbonyl, C₁₋₄alkylcarbonyl, aminocarbonyl, C₁₋₄ alkylaminocarbonyl, nitro, oxazolyl,oxazolyl, pyridyl, dihydropyridyl, tetrahydropyridyl, piperidinyl,thiazinyl, pyrrolyl, imidazolyl, pyrimidinyl, piperazinyl, pyrazolyl,morpholinyl, furanyl, pyranyl, phenyl, C₁₋₄ alkyl substituted phenyl,and Di(C₁₋₄ alkyl) substituted phenyl.

Further, R₃ can be selected from hydrogen, fluorine, chlorine, bromine,iodine, nitro, amino, methyl, ethyl, propyl, isopropyl, new butyl,cyclopropyl, cyclohexyl, halogenated cyclopropyl, halogenatedcyclohexyl, halogenated C₁₋₆ alkyl, C₂₋₄ alkenyl, hydroxyl-substitutedC₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkoxycarbonyl, aminocarbonyl, C₁₋₄alkylaminocarbonyl, Di(C₁₋₄ alkyl)aminocarbonyl, C₃₋₆cycloalkylaminocarbonyl, C₃₋₆ cycloalkoxy, hydroxy-C₁₋₄ alkoxy,halogenated C₁₋₄ alkoxy, amino C₁₋₄ alkyl, amino C₁₋₄ alkoxy, C₁₋₄ alkylsulfone, C₂₋₄ alkenyl sulfone, C₃₋₆ cycloalkyl sulfone, heterocyclicoxy, amino-substituted piperidinyl, N-methylpiperidin-4-carbonyl,piperazine-C₁₋₁₂ alkyl, formamide, and N-methyl piperidine carboxamide.

Further, R₄ can be selected from hydrogen, C₁₋₆ alkyl, halogenated C₁₋₆alkyl, C₁₋₆ alkoxy, halogenated C₁₋₆ alkoxy, cyclopropyl, cyclopentyl,cyclohexyl, halogen substituted C₃₋₆ cycloalkyl, C₁₋₄ alkoxycarbonyl,C₁₋₆ alkylcarbonyl, aminocarbonyl, C₁₋₆ alkylcarbonyl, nitro, amino,C₁₋₃ alkyl substituted amino, Di(C₁₋₃ alkyl) substituted amino,oxazolyl, thiazinyl, pyridyl, dihydropyridyl, tetrahydropyridyl,piperidinyl, thiazinyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazolyl,piperazinyl, morpholinyl, furanyl, pyranyl, phenyl, halogenated phenyl,benzyl, ethyl phenyl, dimethylphenyl, diethylphenyl, methyl (ethyl)phenyl, halogenated phenyl, and halomethylphenyl.

Further, R₅ and R₆ are hydrogen, halogen atoms, methyl, ethyl, and/orpropyl. Preferably, R₅ and R₆ are hydrogen. When R₅ and R₆ are bothhydrogen, there are no other substituents on naphthalene rings exceptdiamides.

Further, R₁ and R₂ together with adjacent ring atoms can form a ringwith 3-8 ring atoms and a substituted ring structure. A preferredstructure is a 4-methyl-piperazinyl group or N-morpholinyl group.

Further, when neither R₁ or R₂ is hydrogen, R₁ and R₂ are both methylgroups.

Further, when one of R₁ and R₂ is hydrogen, the other one can beselected from one of the following groups: methyl, ethyl, propyl, butyl,C₁₋₄ alkyl substituted thiazolyl, thiazinyl, 2-thiazolyl orthiazol-2-yl, C₁₋₄ alkyl substituted phenyl, trifluoromethylphenyl,meta-trifluoromethylphenyl, C₁₋₄ alkyl substituted pyridyl,6-chloro-piperidin-3-yl, 2-chloropyridin-5-yl, isopropyl, cyclopropyl,cyclohexyl, cyclohexane, and C₁₋₄ alkyl substituted cyclohexyl.

Further, R₄ can be selected from the following groups: 4-fluorophenyl,P-fluorophenyl, difluoro substituted phenyl, 3-methylphenyl,M-methylphenyl, P-methylphenyl, O-methylphenyl, ethyl phenyl, propylphenyl, tert-butylphenyl, 2-methoxyphenyl, o-methoxyphenyl,ethoxyphenyl, di(ethoxy)phenyl, butyloxyphenyl, p-methoxyphenyl, methoxyphenyl, meta-trifluoromethylphenyl, P-trifluoromethylphenyl,2,5-dimethoxyphenyl, M-chlorophenyl, P-chlorophenyl, 3,4-dichlorophenyl,trichloro-substituted phenyl, other halogen-substituted phenyl, C₁₋₄alkyl substituted phenyl, C₁₋₄ alkoxy substituted phenyl, and C₂₋₆alkenyl substituted phenyl.

Specifically, the naphthalene diamide compound of the present disclosurecan be one of the compounds in the following table, wherein X and Y areboth carbonyl groups, R₅ and R₆ are hydrogen, and R₃ is hydrogen.

Number R₄

ABC-01 p-fluorophenyl N-methyl-1-piperazinyl ABC-02 p-fluorophenyl2-thiazolimine ABC-03 p-fluorophenyl meta-trifluoromethyl phenylenimineABC-04 p-methoxyphenyl N-methyl-1-piperazinyl ABC-05 m-methylphenylN-methyl-1-piperazinyl ABC-06 o-methoxyphenyl N-methyl-1-piperazinylABC-07 p-fluorophenyl 6-chloro-pyridine-3- methyleneamino ABC-08 methoxyphenyl 6-chloro-pyridine-3- methyleneamino ABC-09 m-methylphenyl6-chloro-pyridine-3- methyleneamino ABC-10 o-methoxyphenyl6-chloro-pyridine-3- methyleneamino ABC-11 p-fluorophenyl N-morpholinylABC-12 p-methoxyphenyl N-morpholinyl ABC-13 m-methylphenyl N-morpholinylABC-14 o-methoxyphenyl N-morpholinyl ABC-15 2,5-dimethoxyphenyl6-chloro-pyridine-3- methyleneamino ABC-16 2,5-dimethoxyphenylN-morpholinyl ABC-17 meta-trifluoromethylphenyl 6-chloro-pyridine-3-methyleneamino ABC-18 meta-trifluoromethylphenyl N-morpholinyl ABC-192,5-dimethoxyphenyl N-methyl-1-piperazinyl ABC-20meta-trifluoromethylphenyl N-methyl-1-piperazinyl ABC-21 p-fluorophenylcyclopropylimine ABC-22 p-fluorophenyl cyclohexylimine ABC-23p-methoxyphenyl cyclohexylimine ABC-24 meta-trifluoromethylphenylcyclohexylimine ABC-26 meta-trifluoromethylphenyl meta-trifluoromethylphenylenimine ABC-27 p-methoxyphenyl cyclopropylimine ABC-28meta-trifluoromethylphenyl cyclopropylimine ABC-29 p-methoxyphenylisopropylimine ABC-30 meta-trifluoromethylphenyl isopropylimine ABC-31p-methoxyphenyl 2-thiazolimine ABC-32 m-methylphenyl 2-thiazolimineABC-33 p-methoxyphenyl meta-trifluoromethyl phenylenimine ABC-34meta-trifluoromethylphenyl 2-thiazolimine ABC-36 p-fluorophenylisopropylimine ABC-37 m-methylphenyl isopropylimine ABC-38o-methoxyphenyl isopropylimine ABC-39 m-chlorophenyl N-morpholinylABC-40 3,4-dichlorophenyl N-morpholinyl ABC-41 m-chlorophenylN-methyl-1-piperazinyl ABC-42 3,4-dichlorophenyl N-methyl-1-piperazinylABC-43 m-chlorophenyl cyclopropylimine ABC-44 3,4-dichlorophenylcyclopropylimine ABC-45 m-chlorophenyl 2-thiazolimine ABC-463,4-dichlorophenyl 2-thiazolimine ABC-47 m-chlorophenyl isopropylimineABC-48 3,4-dichlorophenyl isopropylimine ABC-50 o-methoxyphenyl2-thiazolimine

Further, the naphthalene diamide compound of the present disclosure mayalso be one of the compounds in the following table, wherein X and Y areboth sulfonyl groups or one of them is a sulfonyl group and the other isa carbonyl group, while R₅ and R₆ are hydrogen or a simple alkyl group,and R₃ is hydrogen.

ID X Y R₄

R₅ R₆ ABC-51 sulfonyl carbonyl p-fluorophenyl N-methyl-1-piperazinylmethyl ethyl ABC-52 carbonyl sulfonyl isopropyl methyl ABC-53 sulfonylsulfonyl ethyl isopropyl ABC-54 sulfonyl carbonyl P-fluorophenyl2-thiazolimine methyl ethyl ABC-55 carbonyl sulfonyl P-fluorophenylisopropyl methyl ABC-56 sulfonyl sulfonyl P-fluorophenyl ethyl isopropylABC-57 sulfonyl carbonyl p-fluorophenyl meta-trifluoromethyl methylethyl ABC-58 carbonyl sulfonyl phenylenimine isopropyl methyl ABC-59sulfonyl sulfonyl ethyl isopropyl ABC-60 sulfonyl carbonylp-methoxyphenyl N-methyl-1-piperazinyl methyl ethyl ABC-61 carbonylsulfonyl N-methyl-1-piperazinyl isopropyl methyl ABC-62 sulfonylsulfonyl N-methyl-1-piperazinyl ethyl isopropyl ABC-63 sulfonyl carbonylm-methylphenyl N-methyl-1- methyl ethyl ABC-64 carbonyl sulfonylpiperazinyl isopropyl methyl ABC-65 sulfonyl sulfonyl ethyl isopropylABC-66 sulfonyl carbonyl o-methoxyphenyl N-methyl-1-piperazinyl methylEthyl ABC-67 carbonyl sulfonyl isopropyl methyl ABC-68 sulfonyl sulfonylethyl isopropyl ABC-69 sulfonyl carbonyl p-fluorophenyl 6-chloro- methylEthyl ABC-70 carbonyl sulfonyl pyridine-3- isopropyl methyl ABC-71sulfonyl sulfonyl methyleneamino ethyl isopropyl ABC-72 sulfonylcarbonyl methoxy phenyl 6-chloro- methyl ethyl ABC-73 carbonyl sulfonylpyridine-3- isopropyl methyl ABC-74 sulfonyl sulfonyl methyleneaminoethyl isopropyl ABC-76 sulfonyl carbonyl m-methylphenyl 6-chloro- methylethyl ABC-77 carbonyl sulfonyl pyridine-3- isopropyl methyl ABC-78sulfonyl sulfonyl methyleneamino ethyl isopropyl ABC-79 sulfonylcarbonyl o-methoxyphenyl 6-chloro- methyl ethyl ABC-80 carbonyl sulfonylpyridine-3- isopropyl methyl ABC-81 sulfonyl sulfonyl methyleneaminoethyl isopropyl ABC-82 sulfonyl carbonyl p-fluorophenyl N-morpholinylmethyl ethyl ABC-83 carbonyl sulfonyl N-morpholinyl isopropyl methylABC-84 sulfonyl sulfonyl N-morpholinyl ethyl isopropyl ABC-85 sulfonylcarbonyl p-methoxyphenyl N-morpholinyl methyl ethyl ABC-86 carbonylsulfonyl N-morpholinyl isopropyl methyl ABC-87 sulfonyl sulfonylN-morpholinyl ethyl isopropyl ABC-88 sulfonyl carbonyl m-methylphenylN-morpholinyl methyl ethyl ABC-89 carbonyl sulfonyl N-morpholinylisopropyl methyl ABC-90 sulfonyl sulfonyl N-morpholinyl ethyl isopropylABC-91 sulfonyl carbonyl o-methoxyphenyl N-morpholinyl methyl ethylABC-92 carbonyl sulfonyl isopropyl methyl ABC-93 sulfonyl sulfonyl ethylisopropyl ABC-94 sulfonyl carbonyl 2,5- 6-chloro- methyl ethyl ABC-95carbonyl sulfonyl dimethoxyphenyl pyridine-3-methyleneamino isopropylmethyl ABC-96 sulfonyl sulfonyl ethyl isopropyl ABC-97 sulfonyl carbonyl2,5- N-morpholinyl methyl ethyl ABC-98 carbonyl sulfonyl dimethoxyphenylisopropyl methyl ABC-99 sulfonyl sulfonyl ethyl isopropyl ABC-100sulfonyl carbonyl meta- 6-chloro- methyl ethyl ABC-101 carbonyl sulfonyltrifluoromethylphenyl pyridine-3-methyleneamino isopropyl methyl ABC-102sulfonyl sulfonyl Ethyl isopropyl ABC-103 sulfonyl carbonyl meta-N-morpholinyl methyl ethyl ABC-104 carbonyl sulfonyltrifluoromethylphenyl isopropyl methyl ABC-105 sulfonyl sulfonyl ethylisopropyl ABC-106 sulfonyl carbonyl 2,5- N-methyl-1-piperazinyl methylethyl ABC-107 carbonyl sulfonyl dimethoxyphenyl N-methyl-1-piperazinylisopropyl methyl ABC-108 sulfonyl sulfonyl N-methyl-1-piperazinyl Ethylisopropyl ABC-109 sulfonyl carbonyl meta- N-methyl-1-piperazinyl methylethyl ABC-110 carbonyl sulfonyl trifluoromethylphenyl isopropyl methylABC-111 sulfonyl sulfonyl ethyl isopropyl ABC-112 sulfonyl carbonylp-fluorophenyl cyclopropylimine methyl ethyl ABC-113 carbonyl sulfonylisopropyl methyl ABC-114 sulfonyl sulfonyl ethyl isopropyl ABC-115sulfonyl carbonyl p-fluorophenyl cyclohexylimine methyl ethyl ABC-116carbonyl sulfonyl cyclohexylimine isopropyl methyl ABC-117 sulfonylsulfonyl cyclohexylimine ethyl isopropyl ABC-118 sulfonyl carbonylp-methoxyphenyl cyclohexylimine methyl ethyl ABC-119 carbonyl sulfonylcyclohexylimine isopropyl methyl ABC-120 sulfonyl sulfonylcyclohexylimine ethyl isopropyl ABC-121 sulfonyl carbonyl meta-cyclohexylimine methyl ethyl trifluoromethylphenyl ABC-122 carbonylsulfonyl meta- isopropyl methyl trifluoromethylphenyl ABC-123 sulfonylsulfonyl meta- ethyl isopropyl trifluoromethylphenyl ABC-124 sulfonylcarbonyl meta- m- methyl ethyl ABC-125 carbonyl sulfonyltrifluoromethylphenyl trifluoromethyl isopropyl methyl ABC-126 sulfonylsulfonyl benzylimino ethyl isopropyl ABC-127 sulfonyl carbonyl P-cyclopropylimine methyl ethyl ABC-128 carbonyl sulfonyl methoxyphenylcyclopropylimine isopropyl methyl ABC-129 sulfonyl sulfonylcyclopropylimine ethyl isopropyl ABC-130 sulfonyl carbonyl Meta-cyclopropylimine methyl ethyl ABC-131 carbonyl sulfonyltrifluoromethylphenyl isopropyl methyl ABC-132 sulfonyl sulfonyl ethylisopropyl ABC-133 sulfonyl carbonyl p- isopropylimine methyl ethylABC-134 carbonyl sulfonyl methoxyphenyl isopropylimine isopropyl methylABC-135 sulfonyl sulfonyl isopropylimine ethyl isopropyl ABC-136sulfonyl carbonyl meta- isopropylimine methyl ethyl ABC-137 carbonylsulfonyl trifluoromethylphenyl isopropyl methyl ABC-138 sulfonylsulfonyl ethyl isopropyl ABC-139 sulfonyl carbonyl p- 2-thiazoliminemethyl ethyl ABC-140 carbonyl sulfonyl methoxyphenyl 2-thiazolimineisopropyl methyl ABC-141 sulfonyl sulfonyl 2-thiazolimine ethylisopropyl ABC-142 sulfonyl carbonyl m-methylphenyl 2-thiazolimine methylethyl ABC-143 carbonyl sulfonyl isopropyl methyl ABC-144 sulfonylsulfonyl ethyl isopropyl ABC-145 sulfonyl carbonyl p- meta- methyl ethylABC-146 carbonyl sulfonyl methoxyphenyl trifluoromethyl isopropyl methylABC-147 sulfonyl sulfonyl phenylenimine Ethyl isopropyl ABC-148 sulfonylcarbonyl meta- 2-thiazolimine methyl Ethyl ABC-149 carbonyl sulfonyltrifluoromethylphenyl isopropyl methyl ABC-150 sulfonyl sulfonyl ethylisopropyl ABC-151 sulfonyl carbonyl p-fluorophenyl isopropylimine methylethyl ABC-152 carbonyl sulfonyl isopropyl methyl ABC-153 sulfonylsulfonyl ethyl isopropyl ABC-154 sulfonyl carbonyl m-methylphenylisopropylimine methyl ethyl ABC-155 carbonyl sulfonyl isopropylimineisopropyl methyl ABC-156 sulfonyl sulfonyl isopropylimine ethylisopropyl ABC-157 sulfonyl carbonyl o- isopropylimine methyl ethylABC-158 carbonyl sulfonyl methoxyphenyl isopropyl methyl ABC-159sulfonyl sulfonyl ethyl isopropyl ABC-160 sulfonyl carbonylm-chlorophenyl N-morpholinyl methyl ethyl ABC-161 carbonyl sulfonylN-morpholinyl isopropyl methyl ABC-162 sulfonyl sulfonyl N-morpholinylethyl isopropyl ABC-163 sulfonyl carbonyl 3,4- N-morpholinyl methylethyl ABC-164 carbonyl sulfonyl dichlorophenyl isopropyl methyl ABC-165sulfonyl sulfonyl ethyl isopropyl ABC-166 sulfonyl carbonylm-chlorophenyl N-methyl-1-piperazinyl methyl ethyl ABC-167 carbonylsulfonyl N-methyl-1-piperazinyl isopropyl methyl ABC-168 sulfonylsulfonyl N-methyl-1-piperazinyl ethyl isopropyl ABC-169 sulfonylcarbonyl 3,4- N-methyl-1- methyl ethyl ABC-170 carbonyl sulfonyldichlorophenyl piperazinyl isopropyl methyl ABC-171 sulfonyl sulfonylethyl isopropyl ABC-172 sulfonyl carbonyl m-chlorophenylcyclopropylimine methyl ethyl ABC-173 carbonyl sulfonyl cyclopropylimineisopropyl methyl ABC-174 sulfonyl sulfonyl cyclopropylimine ethylisopropyl ABC-175 sulfonyl carbonyl 3,4- cyclopropylimine methyl ethylABC-176 carbonyl sulfonyl dichlorophenyl isopropyl methyl ABC-177sulfonyl sulfonyl ethyl isopropyl ABC-178 sulfonyl carbonylm-chlorophenyl 2-thiazolimine methyl ethyl ABC-179 carbonyl sulfonyl2-thiazolimine isopropyl methyl ABC-180 sulfonyl sulfonyl 2-thiazolimineethyl isopropyl ABC-181 sulfonyl carbonyl 3,4- 2-thiazolimine methylethyl ABC-182 carbonyl sulfonyl dichlorophenyl isopropyl methyl ABC-183sulfonyl sulfonyl ethyl isopropyl ABC-184 sulfonyl Carbonylm-chlorophenyl isopropylimine methyl ethyl ABC-185 carbonyl sulfonylisopropyl methyl ABC-186 sulfonyl sulfonyl ethyl isopropyl ABC-187sulfonyl carbonyl 3,4- isopropylimine methyl ethyl ABC-188 carbonylsulfonyl dichlorophenyl isopropyl methyl ABC-189 sulfonyl Sulfonyl ethylisopropyl ABC-190 sulfonyl carbonyl o- 2-thiazolimine methyl ethylABC-191 carbonyl sulfonyl methoxyphenyl isopropyl methyl ABC-192sulfonyl sulfonyl ethyl isopropyl

The present disclosure also provides a process for preparation of thecompounds of Formula I mentioned above.

A method for synthesizing the above naphthalene diamide compound,comprising:

-   -   Substituting aromatic acid or other organic carboxylic acid in a        solvent of dichloromethane and participating in the reaction,        catalyzing with a small amount of DMF, stirring the reaction for        several hours to form a series of acid chloride (the first        compound (1) in the following reaction scheme);    -   The acid chloride is then immediately introduced into the        carboxy-substituted naphthylamine. The reaction is carried out        under the catalysis of THF (tetrahydrofuran) and DIEA (N,        N-Di-Isopropylethylamine) to obtain a series of        carboxy-substituted naphthlamide (the following reaction) as the        second compound (2) in this process;    -   The second compound and substituted amine was under stirring        reaction catalyzed by EDCI (1-Ethyl-(3-dimethylaminopropyl)        carbodiimide) and DMAP (4-dimethylaminopyridine) using THF as        the solvent. A series of naphthalene diamide (the third        product (3) shown in the following reaction scheme) was        obtained.    -   The reaction process is shown as follows:

A drug comprises the above compound of Formula I or a pharmaceuticallyacceptable salt or ester with the compound as active ingredients. Anynumber and combination of the above compounds, salt, or ester form canbe selected as active ingredients to produce the drug for treating tumordiseases with antibacterial, antiviral, and anti-inflammatoryproperties.

Compared with the prior scheme, the beneficial effects of the presentdisclosure are shown as follows: the present disclosure provides a novelcompound based on the structure of Formula I, which can be effectivelyapplied to treat and prevent tumor diseases caused by abnormal growth ofvarious human cells.

The present disclosure will be further described in detail by thefollowing case as proof-of-concept examples. However, the scope of thepresent disclosure is not to be limited to the following embodiments.

Example 1, preparation of compound as Formula 1

1.496 g (11 mmol) of m-methylbenzoic acid was placed in a 50 mL roundbottom flask, about 11 mL of dichlorosulfoxide was added, and 3-4 dropsof DMF were added to catalyze the reaction. The mixture was refluxed at80° C. for 3 h. Thin layer chromatography (TLC) was used to follow theprogress of the reaction. After the reaction was completed, the mixturewas cooled to room temperature, and the excess SOCl₂ solvent was removedby rotary evaporation to obtain m-methylbenzoyl chloride.

Example 2, preparation of compound as formula 2

1.496 g (8 mmol) of 6-aminonaphthoic acid was added to the flask,dissolved in THF. 16 mmol of DIEA was added, and the solution wasstirred and kept at 0° C. to obtain the m-methylbenzoyl chloride, whichwas subsequently dissolved in DCM and slowly added dropwise to the abovemixed solution. Thin layer chromatography (TLC) was used to monitor thewhole progress of the reaction. After the reaction was completed, theorganic phase was concentrated by spin-drying to obtain a solid powder,and a small amount of diluted hydrochloric acid acidified solution wasadded, maintaining the pH of solution as weak acidic. The solid wasfiltered and washed 2-3 times with water. The crude compound 2a wasobtained.

Example 3, preparation of compound as formula 3

76.5 mg (0.25 mmol) of Compound 2a, 95 mg (0.5 mmol) of EDCI, and 30 mg(0.25 mmol) of DMAP were dissolved in tetrahydrofuran and stirred atroom temperature for 15 min. Then 35.5 mg (0.25 mmol) of5-aminomethyl-2-chloropyridine was added. The reaction was stirred atroom temperature for about 6 h with the column separation for obtainingthe final product ABC-09.

Example 4, using the synthesis method above by the schemes in examples1-3, the compounds labelled ABC-1 to ABC-192 were separately synthesizedand characterized. The NMR (nuclear magnetic resonance) and MS (massspectrometry) data of the compounds were shown as follows:

ABC-01: ¹H-NMR (DMSO-d₆, 400 MHz): δ 11.05-10.18 (m, 1H), 8.82-7.13 (m,10H), 2.50 (p, J=1.8 Hz, 6H), 2.38 (s, 4H), 2.23 (s, 2H) ppm. HRMS (ESI)m/z: (M+H)⁺ calcd for C₂₃H₂₂FN₃O₂: 390.5; found: 390.2.

ABC-02: ¹H-NMR (DMSO-d₆, 400 MHz): δ 12.73 (s, 1H), 10.62 (s, 1H), 8.74(d, J=1.8 Hz, 1H), 8.56 (d, J=2.0 Hz, 1H), 8.19-7.90 (m, 6H), 7.59 (d,J=3.6 Hz, 1H), 7.46-7.25 (m, 3H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcd forC₂₁H₁₄FN₃O₂S: 390.4; found: 390.3.

ABC-03: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.70 (s, 1H), 10.60 (s, 1H), 8.57(s, 2H), 8.30 (s, 1H), 8.21-7.84 (m, 7H), 7.63 (t, J=8.0 Hz, 1H),7.54-7.33 (m, 3H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcd for C₂₅H₁₆F₄N₂O₂:451.4; found: 451.2.

ABC-04: ¹H-NMR (DMSO-d₆, 400 MHz): δ 8.30 (d, J=2.1 Hz, 1H), 8.00 (s,1H), 7.90-7.68 (m, 5H), 7.46-7.34 (m, 1H), 7.19 (s, 1H), 6.93 (d, J=8.5Hz, 2H), 3.82 (s, 3H), 3.81-2.99 (m, 4H), 2.66-2.12 (m, 4H), 1.19 (s,3H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcd for C₂₄H₂₅N₃O₃: 402.5; found:402.3.

ABC-05: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.48 (s, 1H), 8.52 (d, J=2.0 Hz,1H), 8.12-7.83 (m, 6H), 7.56-7.39 (m, 3H), 3.33 (s, 3H), 2.50 (p, J=1.8Hz, 2H), 2.39 (s, 5H), 2.11 (d, J=99.2 Hz, 4H) ppm. HRMS (ESI) m/z:(M+H)⁺ calcd for C₂₄H₂₅N₃O₂ 386.5; found: 386.3.

ABC-06: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.39 (s, 1H), 8.53 (d, J=2.0 Hz,1H), 3.93 (s, 3H), 3.78 (s, 4H), 2.55-2.49 (m, 5H), 2.19 (d, J=12.8 Hz,5H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcd for C₂₄H₂₅N₃O₃: 402.5; found:402.2.

ABC-07: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.56 (s, 1H), 9.23 (t, J=5.9 Hz,1H), 8.58-8.50 (m, 1H), 8.43 (d, J=3.4 Hz, 2H), 8.15-7.84 (m, 7H),7.58-7.31 (m, 3H), 4.54 (d, J=5.8 Hz, 2H) ppm. HRMS (ESI) m/z: (M+H)⁺calcd for C₂₄H₁₇CIFN₃O₂: 432.9; found: 432.2.

ABC-08: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.39 (s, 1H), 9.23 (t, J=6.0 Hz,1H), 8.47 (d, J=34.1 Hz, 3H), 8.12-7.75 (m, 7H), 7.50 (d, J=8.2 Hz, 1H),7.10 (d, J=8.5 Hz, 2H), 4.54 (d, J=5.8 Hz, 2H), 3.86 (s, 3H) ppm. HRMS(ESI) m/z: (M+H)⁺ calcd for C₂₅H₂₀ClN₃O₃: 444.9; found: 444.3.

ABC-09: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.51 (s, 1H), 9.23 (t, J=5.9 Hz,1H), 8.53 (d, J=1.9 Hz, 1H), 8.43 (d, J=2.8 Hz, 2H), 8.08-7.75 (m, 8H),7.60-7.42 (m, 2H), 4.55 (d, J=5.8 Hz, 2H), 2.43 (s, 3H) ppm. HRMS (ESI)m/z: calcd for C₂₅H₂₀ClN₃O₂: 428.9; found: 428.3.

ABC-10: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.43 (s, 1H), 8.54 (d, J=2.0 Hz,1H), 8.43 (d, J=2.0 Hz, 2H), 7.93 (d, J=1.2 Hz, 2H), 7.88-7.77 (m, 2H),7.68 (dd, J=7.6, 1.8 Hz, 1H), 7.56-7.42 (m, 3H), 7.31-6.95 (m, 3H), 4.55(d, J=5.8 Hz, 2H), 3.93 (s, 3H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcd forC₂₅H₂₀ClN₃O₃: 444.9; found: 444.2.

ABC-11: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.37 (s, 1H), 8.51 (d, J=2.0 Hz,1H), 8.17-7.70 (m, 6H), 7.49 (dd, J=8.4, 1.7 Hz, 1H), 7.39-6.89 (m, 2H),3.86 (s, 3H), 3.48 (d, J=119.1 Hz, 8H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcdfor C₂₃H₂₂N₂O₄: 389.4; found: 389.2.

ABC-12: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.37 (s, 1H), 8.51 (d, J=2.0 Hz,1H), 8.17-7.70 (m, 6H), 7.49 (dd, J=8.4, 1.7 Hz, 1H), 7.39-6.89 (m, 2H),3.86 (s, 3H), 3.48 (d, J=119.1 Hz, 8H) ppm. HRMS (ESI) m/z: (M+H)⁺ calcdfor C₂₃H₂₂N₂O₄: 389.4; found: 389.2.

ABC-13: ¹H-NMR (DMSO-d₆, 400 MHz): δ 8.32 (d, J=2.1 Hz, 1H), 8.07 (s,1H), 7.84-7.56 (m, 5H), 7.43-7.28 (m, 3H), 7.19 (s, 1H), 3.66 (s, 8H),2.39 (s, 3H) ppm. HRMS (ESI) m/z: calcd for C₂₃H₂₂N₂O₃: 373.4; found:373.3.

ABC-14: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.09 (s, 1H), 8.36 (dd, J=7.8, 1.8Hz, 1H), 7.97-7.83 (m, 3H), 7.66-7.45 (m, 3H), 7.31-7.03 (m, 3H), 4.14(s, 3H), 3.76 (s, 8H) ppm.HRMS (ESI) m/z: (M+H)⁺ calcd for C₂₃H₂₂N₂O₄:389.4; found: 389.3.

ABC-15: ¹H-NMR (DMSO-d₆, 400 MHz): δ 10.24 (s, 1H), 8.47 (d, J=40.5 Hz,2H), 8.28 (s, 1H), 7.85 (dd, J=20.3, 7.7 Hz, 4H), 7.59 (d, J=8.9 Hz,1H), 7.41-7.24 (m, 2H), 7.18-6.98 (m, 2H), 6.80 (s, 1H), 4.82-4.59 (m,2H), 4.09 (d, J=2.4 Hz, 3H), 3.88 (t, J=1.8 Hz, 3H) ppm. HRMS (ESI) m/z:calcd for C₂₆H₂₂ClN₃O₄: 474.9; found: 474.4.

A partial nuclear magnetic resonance spectrum is shown in FIG. 1 andFIG. 2, wherein FIG. 1 is the nuclear magnetic resonance spectrum ofcompound ABC-09 and FIG. 2 is the nuclear magnetic resonance spectrum ofcompound ABC-46. The compounds numbered ABC-51 to ABC-192 weresynthesized according to the procedures of Examples 1-3 withquantitative analysis.

Case Study I: Antitumor Cell Activity of Naphthalene Diamides

-   Compounds of Tables 1 and 2 were synthesized in multiple steps    according to the procedure of Examples 1-3 using relevant antitumor    cell activity assays. The compound synthesized above was tested for    IC₅₀ concentration (MIC) against HCT-116, MCF-7, Calu-6 and A549    tumor cells by in vitro cellular activity. The results are shown as    follows.

Case Study II: Cell Proliferation Inhibition Assay

-   Based on MTT method, briefly plating HCT-116, MCF-7 and A549 cells    in a concentration of 2×10⁴/ml with complete culture medium in    96-well plates overnight. The volume for each well was 100 μL. Cells    were treated with compounds in concentrations of 40, 20, 10, 5, 2.5,    1.25 μmol/L, and cultured at 37° C., 5% CO₂ for 48 hours, followed    by adding 20 μL of 5 mg/ml MTT reagent per well and continuing to    culture for 2˜4 h, respectively. As a control, DMSO solvent was    added in an equal volume with concentration of 0.1%. Each sample was    tested as 5 replicate wells. Then the supernatant was discarded, and    DMSO was added in a volume of 150 μL, followed by shaking and mixing    for 15 mins. The absorbance (A) value (A value is proportional to    the number of living cells) is measured by a microplate reader at    the wavelength of 570 nm, and the average value is taken. The    relative cell proliferation inhibition rate (%)=(control group    A₅₇₀—experimental group A₅₇₀)/control group A₅₇₀×100%. The    concentration of 50% inhibition rate (IC₅₀) of the compound was    calculated by the repetition of at least 3 times. The positive    control was used as 5-flucrouracil.

The results (μmol/L) are shown as follows:

ID HCT-116(IC₅₀) MCF-7(IC₅₀) Calu-6(IC₅₀) A549(IC₅₀) ABC-01 ABC-02 10.0ABC-03 ABC-04 ABC-05 10.0 ABC-06 ABC-07 5.8 7.6 ABC-08 10.0 10.9 ABC-093.5 3.2 ABC-10 ABC-11 5.5 3.7 28.104 ABC-12 ABC-13 ABC-14 ABC-15 6.6 3.5ABC-16 ABC-17 3.6 3.2 ABC-18 ABC-19 ABC-20 24.9 2.7 ABC-21 48.5 48.502ABC-22 ABC-23 ABC-24 5 ABC-26 3.5 ABC-27 38.8 2.65 ABC-28 5.0 ABC-29 8.0ABC-30 ABC-31 3.9 ABC-32 5.5 2.9 28.1 14.2 ABC-33 3.0 6.6 ABC-34 5.2 1.6ABC-36 ABC-37 ABC-38 5.0 9 ABC-39 ABC-40 12.4 ABC-41 ABC-42 20.0 7.1 3.7ABC-43 25.3 25.25 ABC-44 5.5 ABC-45 10.0 6.7 12.6 4.3 ABC-46 2.0 6.2 1.6ABC-47 2.5 12.440 ABC-48 3.9 12.629 ABC-50

What is claimed:
 1. A napththalene diamide compound of Formula I:

wherein: X and Y are independently C(═O); R₁ is —CH₂-pyridine, C₃-C₇cycloalkyl, phenyl or thiazole, said R₁ being optionally substituted by1-3 substituents independently selected from halogen and C₁₋₁₂haloalkyl, and R₂ is H, or R₁ and R₂ together with the N atom to whichthey are attached form a piperazine or morpholine ring, said ring beingoptionally substituted by 1-3 substituents independently selected fromhalogen and C₁₋₁₂ alkyl; R₃ is H; R₄ is phenyl optionally substituted by1-3 substituents independently selected from halogen, C₁₋₁₂ haloalkyl,and C₁₋₁₂ alkoxy; and R₅ and R₆ are independently H.
 2. The naphthalenediamide compound of claim 1, wherein R₄ and —N(R₁)(R₂)are as in thefollowing table: Number R₄

ABC-01 p-fluorophenyl N-methyl-1-piperazine ABC-02 p-fluorophenyl2-thiazole imino group ABC-03 p-fluorophenyl Meta-trifluoromethylphenylenimine ABC-04 P-methoxyphenyl N-methyl-1-piperazinyl ABC-05m-methyl phenyl N-methyl-1-piperazinyl ABC-06 o-methoxyphenylN-methyl-1-piperazinyl ABC-07 p-fluorophenyl 6-chloro-pyridine-3-methyleneamino ABC-08 methoxy phenyl 6-chloro-pyridine-3- methyleneaminoABC-09 m-methylphenyl 6-chloro-pyridine-3- methyleneamino ABC-10o-methoxyphenyl 6-chloro-pyridine-3- methyleneamino ABC-11p-fluorophenyl N-morpholinyl ABC-12 p-methoxyphenyl N-morpholinyl ABC-13m-methylphenyl N-morpholinyl ABC-14 o-methoxyphenyl N-morpholinyl ABC-152,5-dimethoxyphenyl 6-chloro-pyridine-3- methyleneamino ABC-162,5-dimethoxyphenyl N-morpholinyl ABC-17 meta-trifluoromethylphenyl6-chloro-pyridine-3- methyleneamino ABC-18 meta-trifluoromethylphenylN-morpholinyl ABC-19 2,5-dimethoxyphenyl N-methyl-1-piperazinyl ABC-20meta-trifluoromethylphenyl N-methyl-l-piperazinyl ABC-21 p-fluorophenylcyclopropylimine ABC-22 p-fluorophenyl cyclohexylimine ABC-23p-methoxyphenyl cyclohexylimine ABC-24 meta-trifluoromethylphenylcyclohexylimine ABC-26 meta-trifluoromethylphenyl meta-trifluoromethylphenylenimine ABC-27 p-methoxyphenyl cyclopropylimine ABC-28meta-trifluoromethylphenyl cyclopropylimine ABC-31 p-methoxyphenyl2-thiazolimine ABC-32 m-methylphenyl 2-thiazolimine ABC-33p-methoxyphenyl meta-trifluoromethyl phenylenimine ABC-34meta-trifluoromethylphenyl 2-thiazolimine ABC-39 m-chlorophenylN-morpholinyl ABC-40 3,4-dichlorophenyl N-morpholinyl ABC-41m-chlorophenyl N-methyl-1-piperazinyl ABC-42 3,4-dichlorophenylN-methyl-1-piperazinyl ABC-43 m-chlorophenyl cyclopropylimine ABC-443,4-dichlorophenyl cyclopropylimine ABC-45 m-chlorophenyl 2-thiazolimineABC-46 3,4-dichlorophenyl 2-thiazolimine ABC-50 o-methoxyphenyl2-thiazolimine.


3. The naphthalene diamide compound of claim 1 wherein —X—N(R₁)(R₂) isin the 2 position on the naphthalene ring and N(R₃)Y—R₄ is in the 6position, or X—N(R₁)(R₂) is in the 3 position on the naphthalene ringand —N(R₃)—Y—R₄ is in the 7 position.
 4. A pharmaceutical compositioncomprising a compound of claim 1 as an active ingredient.
 5. Apharmaceutical composition comprising a compound of claim 2 as an activeingredient.
 6. A pharmaceutical composition comprising a compound ofclaim 3 as an active ingredient.